Mantle cell lymphoma with endobronchial involvement: A case report.

BACKGROUND: Mantle cell lymphoma (MCL) is a subtype of Non-Hodgkin's lymphoma (NHL). MCL frequently affects extranodal sites while endobronchial involvement is uncommon. Only 5 cases of MCL with endobronchial involvement have been previously reported. CASE SUMMARY: A 56-year-old male patient arrived at the hospital complaining of a dry cough. A mass in the right upper lobe of the lung was revealed in Chest computed tomography (CT). Right lung hilar and mediastinal lymphadenopathies were also found by CT scan. The patient was diagnosed with central-type lung cancer with multiple lymph node metastases after positron emission tomography (PET) CT scan examination. The fiber optic bronchoscope examination revealed diffuse neoplasm infiltration in the inlet of the right up lobar bronchus. The patient was finally diagnosed with MCL based on the bronchoscopy and mediastinoscopy biopsy results. CONCLUSION: MCL could masquerade as central type lung cancer. An endobronchial biopsy examination is necessary for the early diagnosis of MCL.

Noninvasive evaluation of hypoxia in rabbit VX2 lung transplant tumors using spectral CT parameters and texture analysis.

AIM: Noninvasive evaluation of hypoxia in rabbit VX2 lung transplant tumors using spectral CT parameters and texture analysis. MATERIALS AND METHODS: Twenty-five VX2 lung transplant tumors of twenty-two rabbits were included in the study. Contrast-enhanced spectral CT scanning in the arterial phase (AP) and venous phase (VP) was performed. Tumors were divided into strong and weak hypoxic groups by hypoxic probe staining results. Spectral CT image-related parameters [70 keV CT value, normalized iodine concentration (NIC), slope of spectral HU curve (λHU)] were measured and the texture analysis on the monochromatic images was performed. Imaging parameters and texture features between tumors with different hypoxic degrees were compared and their diagnostic efficacies for predicting hypoxia in lung cancers were analyzed using receiver operating characteristic (ROC) curve. RESULTS: NIC in VP and λHU in VP of the strong hypoxic group were significantly higher than those in the weak hypoxic group (p < 0.05). For the texture features, entropy in VP and kurtosis in AP were significantly different between the two hypoxic groups. According to ROC analysis, λHU in VP had a better diagnostic ability for predicting hypoxia in tumors [Area Under Curve (AUC): 0.883, sensitivity: 85.7%, specificity: 100%]. The combination of four features improved AUC to 0.955. CONCLUSION: NIC in VP, λHU in VP, entropy in VP and kurtosis in AP have certain values in predicting tumor hypoxia and a combination of image parameters and texture features improves diagnostic efficiency.

Development and validation of a multivariable predictive model for EGFR gene mutation status in patients with lung adenocarcinoma.

Detection of epidermal growth factor receptor (EGFR) is one real dilemma owing to the non-sufficient tissue for testing EGFR mutations in lung adenocarcinoma. A model for predicting EGFR mutations would be helpful for clinical decisions in those patients. A retrospective cohort of 1,196 patients diagnosed with lung adenocarcinoma was investigated between December 1, 2017, and December 31, 2019, in Renji Hospital, Shanghai, China. All patients were tested for EGFR mutations (amplification refractory mutation system, n=1,144; next-generation sequencing, n=52). Of 1,196 patients with lung adenocarcinoma, 944 met the inclusion criteria. A nomogram model was developed based on 567 patients and validated in 377 patients. Variables associated with EGFR mutations were age, sex, smoking history, lepidic predominant subtype, solid predominant subtype, mucinous adenocarcinoma, Ki67 expression, lobulation, solid texture in radiology, and pleural retraction. The nomogram based on the model performed well in the development group (c-index 0.789, 95% CI: 0.751-0.827), and the validation group (c-index 0.809, 95% CI: 0.771-0.847). At the probability cut-point of 0.7, the diagnostic efficiency was 82.7% in patients with NGS liquid biopsy. Decision curve analysis further confirmed the clinical usefulness of the nomogram, which showed that predicting the EGFR mutations probability applying this nomogram would be better than having all patients or none patients use this nomogram. A high probability group (>0.7) by nomogram model may suggest a high possibility of EGFR mutation, if tissue is limited, NGS-based ctDNA with liquid biopsy could be implemented effectively.

USP12 downregulation orchestrates a protumourigenic microenvironment and enhances lung tumour resistance to PD-1 blockade.

Oncogenic activation of KRAS and its surrogates is essential for tumour cell proliferation and survival, as well as for the development of protumourigenic microenvironments. Here, we show that the deubiquitinase USP12 is commonly downregulated in the KrasG12D-driven mouse lung tumour and human non-small cell lung cancer owing to the activation of AKT-mTOR signalling. Downregulation of USP12 promotes lung tumour growth and fosters an immunosuppressive microenvironment with increased macrophage recruitment, hypervascularization, and reduced T cell activation. Mechanistically, USP12 downregulation creates a tumour-promoting secretome resulting from insufficient PPM1B deubiquitination that causes NF-κB hyperactivation in tumour cells. Furthermore, USP12 inhibition desensitizes mouse lung tumour cells to anti-PD-1 immunotherapy. Thus, our findings propose a critical component downstream of the oncogenic signalling pathways in the modulation of tumour-immune cell interactions and tumour response to immune checkpoint blockade therapy.

In vivo therapeutic success of MicroRNA-155 antagomir in a mouse model of pulmonary fibrosis induced by bleomycin.

BACKGROUND/AIMS: MicroRNAs (miRNAs) play critical regulatory roles in the pathogenesis of pulmonary fibrosis. The aim of this study was to explore whether miRNA antagomirs could serve as potential therapeutic agents in interstitial lung diseases. METHODS: A mouse model of pulmonary fibrosis was established by intratracheal injection of bleomycin (BLM). Using microarray analysis, up-regulated miRNAs were identified during the development of pulmonary fibrosis. miR-155 was chosen as the candidate miRNA. Fifteen mice were then randomized into the following three groups: BLM + antagomiR-155 group, treated with BLM plus intravenously injected with antagomiR-155; BLM group, treated with intratracheal BLM plus phosphate-buffered saline (PBS); and a control group, treated with PBS only. Lung tissues were collected for histopathological analysis, hydroxyproline measurement, and Western blotting. Enzyme-linked immunosorbent assays were used for the measurement of cytokines associated with pulmonary fibrosis. RESULTS: Histological changes and hydroxyproline levels induced by BLM were significantly inhibited by antagomiR-155. The levels of interleukin 4 (IL-4) and transforming growth factor-ß (TGF-ß) expression were increased after BLM treatment. However, miR-155 silencing decreased the expression of IL-4, TGF-ß, and interferon-γ. TGF-ß-activated kinase 1/mitogen-activated protein kinase kinase kinase 7 (MAP3K7)-binding protein 2 (TAB2) of the mitogen-activated protein kinase (MAPK) signaling pathway, was activated by BLM and inhibited by in vivo silencing of miR-155 via antagomiR-155. CONCLUSION: In vivo treatment with antagomiR-155 alleviated the pathological changes induced by BLM and may be a promising therapeutic strategy for pulmonary fibrosis.

The associations among quantitative spectral CT parameters, Ki-67 expression levels and EGFR mutation status in NSCLC.

Dual-energy spectral computed tomography (DESCT) is based on fast switching between high and low voltages from view to view to obtain dual-energy imaging data, and it can generate monochromatic image sets, iodine-based material decomposition images and spectral CT curves. Quantitative spectral CT parameters may be valuable for reflecting Ki-67 expression and EGFR mutation status in non-small-cell lung cancer (NSCLC). We investigated the associations among the quantitative parameters generated in DESCT and Ki-67 expression and EGFR mutation in NSCLC. We studied sixty-five NSCLC patients with preoperative DESCT scans, and their specimens underwent Ki-67 and EGFR evaluations. Statistical analyses were performed to identify the spectral CT parameters for the diagnosis of Ki-67 expression and EGFR mutation status. We found that tumour grade and the slope of the spectral CT curve in the venous phase were the independent factors influencing the Ki-67 expression level, and the area under the curve (AUC) of the slope of the spectral CT curve in the venous phase in the receiver operating characteristic analysis for distinguishing different Ki-67 expression levels was 0.901. Smoking status and the normalized iodine concentration in the venous phase were independent factors influencing EGFR mutation, and the AUC of the two-factor combination for predicting the presence of EGFR mutation was 0.807. These results show that spectral CT parameters may be useful for predicting Ki-67 expression and the presence of EGFR mutation in NSCLC.

Bronchopleural fistula following a video-assisted thoracoscopic surgery lobectomy after neoadjuvant therapy of pembrolizumab: a case report and literature review.

Lung cancer has the highest morbidity and mortality worldwide among the malignant tumors. The treatment of lung cancer was difficult in the decade years. Currently, the advent of immune checkpoint inhibitors (ICIs) has changed the pattern of lung cancer treatment. Programmed death-ligand 1 (PD-L1) inhibitors, such as pembrolizumab, plus platinum-based chemotherapy is the preferred treatment modality for advanced or metastatic non-small cell lung cancer (NSCLC) patients. The success of pembrolizumab in lung cancer has increased interest in expanding the use of neoadjuvant treatment. Immune-related adverse events (irAEs) are the most common adverse reactions in immunotherapy. The balance between the benefits and risks is crucial in this setting. Video-assisted thoracoscopic surgery (VATS) is a routine procedure of resectable NSCLC treatment. It appears to favor low postoperative complication rate. The prolonged air leakage (PAL) is the most common complication after VATS, and the bronchopleural fistula (BPF) is the most serious complication. The management of adverse events after VATS, especially in the setting of immune therapy, need to be raised. Here, we report a case of BPF following VATS lobectomy, which firstly presented the treatment-related adverse event with neoadjuvant combination therapy of pembrolizumab plus cisplatin/pemetrexed. Literature on novel neoadjuvant immunotherapy was also reviewed in the present study.

Diffusion-weighted MRI in solitary pulmonary lesions: associations between apparent diffusion coefficient and multiple histopathological parameters.

Apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) has gained wide attention as potential tool for differentiating between malignant and benign solitary pulmonary lesions (SPLs). The overall effects of multiple histopathological parameters on ADC have not been elucidated, which may help to explain the overlapping of ADC between malignant and benign SPLs. The study sought to explore associations between ADC and histopathological parameters in SPLs, and to compare diagnostic capability of ADC among different types of SPLs. Multiple histopathological parameters (cell density, nuclear-to-cytoplasm ratio, necrotic fraction, presence of mucus and grade of differentiation) were quantified in 52 malignant and 13 benign SPLs with surgical pathology available. Cell density (ß = -0.40) and presence of mucus (ß = 0.77) were independently correlated with ADC in malignant SPLs. The accurate diagnosis rate of squamous carcinomas, adenocarcinomas without mucus and malignant tumors with mucus was 100%, 82% and 0%, respectively. Our study suggested that cell density and presence of mucus are independently correlated with ADC in malignant SPLs. Squamous carcinoma maybe more accurately diagnosed as malignancy by ADC value. Malignant SPLs with mucus and adenocarcinomas with low cell density should be kept in mind in differentiating SPLs using ADC because of insufficient diagnostic capability.

Lesion based diagnostic performance of dual phase 99mTc-MIBI SPECT/CT imaging and ultrasonography in patients with secondary hyperparathyroidism.

BACKGROUND: We aimed to evaluate the diagnostic performance of 99mTc-MIBI SPECT/CT and ultrasonography in patients with secondary hyperparathyroidism (SHPT), and explored the factors that affect the diagnostic performance. METHODS: 99mTc-MIBI SPECT/CT and ultrasonography were performed in 50 patients with SHPT within 1 month before they underwent surgery. Imaging results were confirmed by the pathology. Pearson correlation analysis was used to determine the correlation of PTH level with clinical data. The optimal cutoff value for predicting positive 99mTc-MIBI results was evaluated by ROC analysis in lesions diameter. RESULTS: Forty-nine patients had a positive 99mTc-MIBI imaging results and 39 patients had positive ultrasonography results. The sensitivities of 99mTc-MIBI and ultrasonography were 98.00% and 78.00%, respectively. A total of 199 lesions were resected in 50 patients. Among them, 183 lesions were proved to be parathyroid hyperplasia. On per-lesion basis analysis, the sensitivity and specificity of 99mTc-MIBI and ultrasonography were 59.34% and 75.00% vs 46.24% and 80.00%, respectively. The Pearson correlation analysis showed that the serum AKP and PTH level had a significant linear association (r = 0.699, P < 0.001). The lesion diameter was a statistically significant predictive factor in predicting positive 99mTc-MIBI SPECT/CT. The optimal cutoff value for predicting positive 99mTc-MIBI results evaluated by ROC analysis in lesions diameter was 8.05 mm. CONCLUSION: Dual phase 99mTc-MIBI SPECT/CT imaging had a higher sensitivity in patients with SHPT than ultrasonography. Therefore, using 99mTc-MIBI positioning the lesion could be an effective method pre-surgical in patients with SHPT.

Assessment and prognostic analysis of EGFR, HER2, and HER3 protein expression in surgically resected gastric adenocarcinomas.

AIM: To investigate the significance of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER)2, and HER3 expression on survival outcomes in Chinese gastric cancer patients. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded specimens from 121 patients who underwent gastrectomy at Shanghai Renji Hospital from 2007-2010 were retrospectively examined. Fluorescence in situ hybridization and immunohistochemistry techniques were used to identify gene amplification and protein overexpression. Correlations between the expression or amplification of HER family genes and clinicopathological parameters were then determined using statistical analysis. RESULTS: EGFR protein overexpression, an increase in HER2 copy number and gene amplification, and HER3 protein overexpression were identified in 33.1%, 17.4%, and 62.0% of samples, respectively. Statistical analysis showed a significant association between EGFR expression and tumor invasion depth or tumor stage. HER2 was also shown to be significantly associated with the tumor grade. In addition, EGFR protein overexpression was found to be significantly associated with worse overall survival (P=0.03). CONCLUSION: The HER family members showed a high expression in gastric cancer. EGFR protein expression was associated with overall survival.